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Expert Q&A

What are the long-term brain effects of Xanax?

Asked by Grant, Columbus, Ohio

What are the long-term effects of Xanax use on the brain if taken exactly as directed? It seems that my mind feels like it is stuck in the mud, hazy and there is a feeling of a disconnect with the world sometimes. Ultimately, how long does it take for your brain and mind to return to "normal" function?

Expert answer

Dear Grant, I thought I would address your questions this week because they are great examples of important issues for which we do not have settled answers. I think it's good sometimes for people to get a better sense of how many things psychiatrists and other physicians don't know. Just as an aside, the most common reasons for us not knowing the answers to important questions are that the answers are too complicated to yield easy information or that no one has been willing to put in the time and money to do the studies necessary to provide certainty.

We know a great deal about the short-term effects of Xanax (generic name is alprazolam) and other benzodiazepine medications on the brain. By blocking the benzodiazepine site on gamma receptors in the brain, these medications hyperpolarize neurons (i.e. brain cells). When hyperpolarized, neurons don't fire as often, which makes parts of the brain that induce feelings of anxiety and fear less active. When these brain areas are turned down, people feel calmer and are less likely to become fearful, agitated or anxious. Unlike antidepressants, which take days to weeks to turn down brain anxiety centers (and to show clinical effect), Xanax and other benzodiazepines produce immediate relief.

Benzodiazepines are hugely effective, but they have two major drawbacks. First, over time the brain adjusts to their activity, so that if they are stopped suddenly, brain activity can overshoot normal. When this happens, people show withdrawal symptoms, such as high blood pressure, shaking and intense anxiety. When severe, benzodiazepine withdrawal can produce death. Drugs such as benzodiazepines that can produce these types of withdrawal problems are said to produce "physiological dependence," which is a fancy word for meaning they can be addictive. A second drawback is that the danger of addiction to these agents is further increased by the fact that they work so quickly. Bad anxiety is probably the single most miserable emotional state humans can experience. It is truly a living hell. For people who struggle with anxiety, the fact that benzodiazepines work so quickly greatly increases the risk for developing psychological dependence.

Compared with other benzodiazepines, Xanax has an additional problem. It has a very short half-life, which in practical terms means that it goes in and out of the body very quickly. Because of this, many people will begin to experience subtle withdrawal symptoms between doses, which really can increase the addictive potential of this medication. Like most other psychiatrists, I dislike Xanax for this reason and will often try to switch long-term Xanax users to one of the other benzodiazepines that has a longer half-life and less liability for producing patterns of rising and falling anxiety across the day.

It has been folk wisdom within medicine that using benzodiazepines for a long time is a bad idea. They were believed to make people mentally slow. However, recent years have produced a number of studies comparing people who have taken a benzodiazepine for years nonstop with people who have never taken a benzodiazepine. Most of these studies show no ill effects of benzodiazepines on either mental functioning or physical health. On the other hand, chronic anxiety is a life-destroyer of the first order, and is at least as big a risk factor for suicide as is depression.

So, we don't know how the long-term use of benzodiazepines changes the brain, nor do we know how long it would take for all effects of these medications to go away. Withdrawal-type symptoms typically resolve in a week or two depending on the half-life of the specific benzodiazepine involved, which suggests that at a gross level, the brain returns to normal fairly quickly. But whether subtler changes persist is unknown.

In your particular case, Xanax might be producing the disconnected, muddy, hazy feelings against which you struggle. If these feelings coincide with each dose of Xanax and improve as the hours pass, it is a good bet that Xanax is the culprit. But it is also quite possible that your cognitive symptoms are part of an underlying psychiatric condition. If these symptoms improve after each dose of Xanax, this is the more likely scenario. Many conditions that produce impaired thinking and feeling are not spotted by traditional medical exams or laboratory tests, so you should not be surprised or overly concerned that there is a disconnect between your symptoms and apparent good health.

Let me make a final comment. You use the phrase "exactly as prescribed" and this is a very important point. The vast majority of people who take benzodiazepines for extended periods are highly compliant and follow doctors' orders closely. Indeed, in my experience many anxious patients who would benefit from benzodiazepine treatment are so worried about addiction and other problems that they deny themselves an important potential pathway to well-being. But the other extreme is even more problematic. Although in my experience benzodiazepines do not have the addiction potential of something like opiate pain pills, they can cause significant trouble when abused. Hence the importance of taking "exactly as prescribed."

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